Prosthetic devices or prostheses are commonly used in medical procedures replacing or augmenting defective organs in mammals and humans, in particular, and are numerous and diverse in structure and application. Examples of prostheses include artificial joints, valve replacements, skin grafts, vascular grafts, shunts, plates and contact and intraocular lenses. Typically, prosthetic devices comprise natural and/or synthetic material which are abrasive on the cellular level. Various prostheses in current use or in experimental use comprise metals, ceramics, silicone rubbers, polyesters, polyurethanes and/or polysulfones. Synthetic polymers, such as polymethylmethacrylate (PMMA) and hydroxyethylmethacrylate (HEMA), for example, are preferred polymers for prosthetic use in general and contact lenses and intraocular lenses in particular.
PMMA, for example, has several beneficial characteristics for such prosthetic use, including excellent light transmission, good optical clarity, resistance to fluid diffusion and in vivo deterioration, ease in processing (injection molding or machining, for example) and ease in implantation, such as an intraocular lens, an artificial joint and other implantable prostheses.
Typical lens prostheses, for example, are manufactured by machining, which leaves circular lathe marks or grooves visible at even relatively low magnification. These machining remnants render the lens unusable until the surface is smoothed, typically by a mechanical polishing process. However, the conventional polishing process generally takes several days to complete, has a failure rate in excess of 30% and fails to produce a microscopically smooth surface.
Abrasive prostheses, especially those which are implanted, can cause tissue irritation, edema and scarring. For example, posterior lens capsule opacification is a prevalent problem among those patients who have received intraocular lens implants comprising conventionally polished PMMA and other similar materials.
It is desirable to modify the surface properties of such abrasive materials without changing the beneficial characteristics thereof by developing a smooth surface thereby discouraging tissue adhesion and inhibiting cellular growth. Prostheses which do not promote tissue adhesion and do not inhibit cellular growth and which are not otherwise toxic to living systems may be considered "biocompatible." Surface modification to develop a biocompatible surface should be resistant to deterioration over time and should have no adverse effects on tissues and cells with which the surface modified material comes in contact.
Those skilled in the art have long recognized the need for biocompatible, surface modified materials for use in prosthetic devices and other materials. For example, U.S. Pat. No. 3,961,379 discloses a bioimplantable device manufactured from a cross-linked, swollen, hydrophilic polymer. These modified polymers must be solid and must be swellable by fluid swelling substances. Once swollen, the solid polymer is polymerized with a modifying substance by, for example, high energy particle radiation.
U.S. Pat. No. 4,189,364 discloses hydrophilic polymers formed in situ by irradiating a mixture of hydroxyalkyl methacrylate and a cross-linking agent. This patent discloses a process for forming hydrophilic polymer articles or hydrophilic polymer coatings on other substrates, such as glass or plastic, by polymerizing a hydrophilic monomer system by high energy particulate irradiation, such as accelerated electrons or nuclear particles including neutrons, protons, alpha, beta and/or gamma particles.
Radiation-induced grafting of acrylic acid onto other polymer films is disclosed by Gazard, M. et al., "Lithographic Technique Using Radiation-Induced Grafting of Acrylic Acid Into Poly(Methyl Methacrylate) Films," Polymer Engineering and Science, 20:16 (1980). Gazard et al. disclose that, under ionizing radiation, polymers undergo changes in their properties, especially in their solubility. Ionizing radiation of polymers leads to the formation of free radicals and other intermediates, which may be used to initiate the grafting of a monomer to produce a grafted copolymer with properties different from those of the initial polymer. For example, irradiated PMMA, onto which acrylic acid is grafted produces a graft copolymer which is insoluble in the solvents of PMMA.
U.S. Pat. No. 2,999,056 also discloses that an unsaturated organic acid may be attached to a shaped polymeric structure by ionizing radiation.
Other methods of altering the surface of polymeric objects include exposing the surface of a polymeric article to low temperature plasma or an electrically charged gaseous atmosphere, followed by contacting the surface of the polymeric article with a surface modifying compound as described, for example, in U.S. Pat. No. 4,344,981. This two-step method is generally called plasma-induced coating. Plasma induction has been described generally in U.S. Pat. No. 4,328,257, Yasuda, "Plasma for Modification of Polymers," J. Macromol. Sci. C. Chem., 10(3):383 (1978), Mittal, "Interfacial Chemistry and Adhesion: Recent Developments and Prospects," Pure & Appl. Chem., 52:1295 (1980), Akovali, G. and Hasirci, N., "Polymerization of Hexamethyldisiloxane by Plasma on Activated Charcoal: Investigation of Parameters," J. Appl. Polymer Sci., 29:2617 (1984) and Liu, W. T. et al., "Polymethyl Methacrylate Resist Sensitivity Enhancement in X-Ray Lithography by In Situ Polymerization," Appl. Phys. Lett., 44:973 (1984), for example.
Ionized vapor or plasma discharge is typically created in a vacuum chamber in which the object to be modified is placed. The plasma discharge conditions the surface by creating free radicals and/or ions. It is known, for example, that exposing the surface of an object to plasma discharge, such as an oxygen plasma, enhances the wettability or hydrophilicity of such a surface. However, such treatment is only temporary. U.S. Pat. Nos. 3,925,178; 3,944,709; 4,072,769; 4,096,315; 4,122,942; 4,123,308; 4,131,691; 4,137,365; 4,214,014 and 4,478,873 disclose examples of polymers whose surface characteristics have been modified by a plasma discharge.
Plasma discharge treatment may also be used to prepare an object for the attachment or grafting of a compound or material to the plasma discharge treated object. For example, a plasma discharge step may be used to condition the surface for grafting by creating free radicals to which a compound or material may be grafted. Such compounds or materials are generally called surface modifiers. Knight, P. M. et al., in "Surface Modification of Intraocular Lenses to Reduce Corneal Endothelial Damage," Am. Intra-ocular Implants Soc. J., 5:123 (1979) disclose one example of a polymer object having a surface modifier attached thereto using gamma irradiation and radio frequency (RF) gas plasma treatment to generate free radicals on the surface of a PMMA intraocular lens followed by polymerizing hydrophilic monomers, in particular, HEMA and vinyl pyrrolidone, as a coating on the surface of the lens. While the coated surfaces exhibited enhanced hydrophilicity, the coated surfaces were not stable when boiled to sterilize them. Surface modification by gamma radiation followed by polymerization on the surface, on the other hand, remained intact through several hours of boiling. However, such coated PMMA surfaces were damaging to rabbit endothelial cells and surfaces coated with dissolvable coatings, such as polyvinyl acetate, were preferred.
Another example of a surface treated polymer is disclosed in U.S. Pat. No. 4,312,575. This patent discloses a soft, highly oxygen permeable, hydrophobic polymeric lens which has on its surface an ultra-thin, optically clear, permeable barrier coating which is the reaction product resulting from a glow discharge polymerization process conducted in a hydrocarbon or halogenated hydrocarbon gaseous atmosphere. While the plasma discharge process, itself, results in a hydrophilic surface, subsequent exposure to a glow discharge atmosphere of oxygen or ambient oxygen yields a still more hydrophilic surface.
U.S. Pat. No. 4,409,258 discloses a method for rendering contact lenses hydrophilic by bombarding the lens, which may be PMMA or silicone, with a positive ion beam generated by a plasma discharge, such as an oxygen plasma. The lens is thereafter hydrated, preferably at an elevated temperature.
Examples of surface treated polymeric lenses for use in humans are included in U.S. Pat. No. 3,880,818. This patent discloses a soft contact lens that is flexible and physiologically compatible, which is made by manufacturing a hard, inflexible prepolymer, such as a hard acrylic acid-type polymer, and reacting the inflexible prepolymer with an alcohol to esterify pendant carboxyl groups with alkyl groups, hydroxy alkyl groups or alkoxyalkyl groups, containing no more than eleven carbon atoms.
U.S. Pat. No. 4,143,949 discloses a discharge polymerization and coating process for making a hydrophilic contact lens from an oxygen permeable, hydrophobic polymer. The hydrophobic lens is placed in a glow discharge apparatus containing an atmosphere comprising a polymerizable organic monomer, such as hydroxyalkyl acrylate or methacrylate, glycidyl methacrylate, propylene oxide or N-vinyl-2-pyrrolidone, where the glow discharge is used to polymerize the monomer onto the surface of the contact lens.
Other examples of surface treated polymeric objects include U.S. Pat. Nos. 3,228,741; 3,925,178; 3,959,105; 3,985,697; 4,055,378; 4,277,595; 4,405,773; 4,430,458; 4,463,148; and 4,731,080. U.S. Pat. No. 4,731,080, for example, discloses a coated intraocular lens having a hydrophobic cross-linked vinyl-containing silicone polymer placed on the lens surface in solution.
It would be desirable to have a biocompatible, surface modified material and a method for producing the same, where the surface modification is substantially permanent, results in a smooth surface on the cellular level and where the surface modified material may be used, inter alia, as a prosthetic device in mammals. One such method is disclosed in our co-pending U.S. patent application Ser. No. 07/342,270, filed Apr. 24, 1989, the disclosure of which is incorporated herein by reference.